scholarly journals 1012. Neutrophil Function Enhanced by Recombinant Interferon-Gamma in Newborns

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S597-S597
Author(s):  
Ricardo Castillo-Galvan ◽  
Nicole Soper ◽  
Monique Bennett ◽  
Isaac Thomsen
Keyword(s):  
Preterm Infants ◽  
Interferon Gamma ◽  
Bacterial Infections ◽  
Fungal Infections ◽  
Three Dimensional ◽  
Neutrophil Function ◽  
Term Infant ◽  
Term Infants ◽  
Recombinant Interferon

Abstract Background Functional differences exist between neonatal and adult neutrophils. The incidence of infection is higher in preterm infants, and the severity of the immune impairment on the neonatal neutrophils is inversely related to gestational age. In order to recognize and combat life-threatening infections, neonates rely predominantly on the innate immune system.Neutrophils are an essential component of innate immunity, and they are the first responders against bacterial and fungal infections. Sepsis continues to be a prominent cause of neonatal mortality, especially among preterm infants. Recombinant interferon-gamma (IFNγ) effects on the immune system have included the upregulation of TLRs expression and stimulation of phagocytosis. They have been shown to reduce severe infections in children with chronic granulomatous disease. Methods After the protocol was IRB approved, we enrolled term infants in their first 48 hours of life (Table 1). We then obtained free flow whole-blood samples through venipuncture from the cephalic vein. Samples were incubated with and without IFNγ for 24 hours. Isolation of unperturbed neutrophils using immunomagnetics was performed for a final concentration of 1x106/mL. We then assessed the neutrophil-bacterial interaction using fluorescent GFP-Staphylococcus aureus, and quantified neutrophil killing function on a novel assay involving fibrin matrix as a more physiologic and three-dimensional (3D) environment than standard in vitro or culture-based assays. We evaluated normalized progressive ratios, 20μL/80μL, 30μL/70μL, 40μL/60μL of Neutrophil/GFP-S aureus respectively.Table 1 Results On the 20 samples, we observed significant differences demonstrating a considerably enhanced phagocytosis on those samples with the addition of IFNγ(p< 0.0001, Table 2 and Figures 1-3). Conclusion The phagocytic ability of neonatal neutrophils was greatly enhanced by the addition of IFNγ in term infant blood. Ongoing work will determine whether this remains true for preterm-infant neutrophils and will further delineate mechanisms of these differences. We recognized an opportunity for interferon-based immunomodulation in certain situations on this population at high risk for invasive bacterial infections. Disclosures Ricardo Castillo-Galvan, MD MPH, Karius Inc. (Consultant) Isaac Thomsen, MD, MSCI, Horizon Therapeutics (Consultant)

scholarly journals Mammary gland 3D cell culture systems in farm animals

2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Laurence Finot ◽  
Eric Chanat ◽  
Frederic Dessauge
Keyword(s):  
Cell Culture ◽  
Mammary Gland ◽  
Bacterial Infections ◽  
Three Dimensional ◽  
3D Cell Culture ◽  
Farm Animals ◽  
Culture Systems ◽  
Cell Culture Systems

AbstractIn vivo study of tissue or organ biology in mammals is very complex and progress is slowed by poor accessibility of samples and ethical concerns. Fortunately, however, advances in stem cell identification and culture have made it possible to derive in vitro 3D “tissues” called organoids, these three-dimensional structures partly or fully mimicking the in vivo functioning of organs. The mammary gland produces milk, the source of nutrition for newborn mammals. Milk is synthesized and secreted by the differentiated polarized mammary epithelial cells of the gland. Reconstructing in vitro a mammary-like structure mimicking the functional tissue represents a major challenge in mammary gland biology, especially for farm animals for which specific agronomic questions arise. This would greatly facilitate the study of mammary gland development, milk secretion processes and pathological effects of viral or bacterial infections at the cellular level, all with the objective of improving milk production at the animal level. With this aim, various 3D cell culture models have been developed such as mammospheres and, more recently, efforts to develop organoids in vitro have been considerable. Researchers are now starting to draw inspiration from other fields, such as bioengineering, to generate organoids that would be more physiologically relevant. In this chapter, we will discuss 3D cell culture systems as organoids and their relevance for agronomic research.

scholarly journals Platelets in the neonatal period: developmental differences in platelet production, function, and hemostasis and the potential impact of therapies

Hematology ◽  
2012 ◽  
Vol 2012 (1) ◽  
pp. 506-511 ◽  
Author(s):  
Martha Sola-Visner
Keyword(s):  
Preterm Infants ◽  
Neonatal Intensive Care ◽  
Developmental Differences ◽  
Full Term ◽  
Term Infants ◽  
Platelet Production ◽  
Primary Hemostasis ◽  
Wall Interaction ◽  
And Function

Abstract Thrombocytopenia is a common problem among sick neonates admitted to the neonatal intensive care unit. Frequently, platelet transfusions are given to thrombocytopenic infants in an attempt to decrease the incidence or severity of hemorrhage, which is often intracranial. Whereas there is very limited evidence to guide platelet transfusion practices in this population, preterm infants in the first week of life (the highest risk period for bleeding) are nearly universally transfused at higher platelet counts than older infants or children. To a large extent, this practice has been influenced by the observation that neonatal platelets are hyporeactive in response to multiple agonists in vitro, although full-term infants exhibit normal to increased primary hemostasis. This apparently paradoxical finding is due to factors in the neonatal blood that enhance the platelet-vessel wall interaction and counteract the platelet hyporeactivity. Relatively few studies have evaluated the platelet function and primary hemostasis of preterm infants, the subset of neonates at highest risk of bleeding and those most frequently transfused. Current understanding of platelet production and function in preterm and full-term neonates, how these factors affect their response to thrombocytopenia and their primary hemostasis, and the implications of these developmental differences to transfusion medicine are reviewed herein.

Phase I trial of recombinant interferon gamma in cancer patients.

1986 ◽  
Vol 4 (2) ◽  
pp. 137-146 ◽  
Author(s):  
S Vadhan-Raj ◽  
A Al-Katib ◽  
R Bhalla ◽  
L Pelus ◽  
C F Nathan ◽  
...  
Keyword(s):  
Interferon Gamma ◽  
Phase 1 ◽  
Rest Period ◽  
Lymphocytic Leukemia ◽  
Fixed Dose ◽  
Rapid Decline ◽  
Recombinant Interferon ◽  
Advanced Malignancy

Interferon gamma (IFN-gamma) is a lymphokine with potent in vitro effects on cell growth and immune function. We have investigated the effects of rIFN-gamma (sp act approximately 2 X 10(7) U/mg, purity greater than 99%) in 16 evaluable patients with advanced malignancy in a phase 1 trial. Patients were treated with six-hour intravenous (IV) infusions daily, five days a week for 2 weeks. After a 2-week rest period, the IV treatment cycle was repeated. Responders were maintained on repeated IV treatment cycles or daily intramuscular (IM) injections. Patients were entered at fixed dose levels of 0.1, 0.5, or 1.0 mg/m2/d. The maximum safely tolerated dose was 0.5 mg/m2. The most common side effects were constitutional symptoms, including fever, chills, fatigue, and myalgias. Reversible and transient increases in hepatic transaminase and decrease in granulocyte counts were seen. Treatment was associated with a dose-dependent increase in serum levels of beta 2 microglobulin. Partial responses (PRs) were observed in one patient with Hodgkin's disease and one patient with chronic lymphocytic leukemia. Fairly constant levels of serum IFN were found at four and six hours during infusion, followed by a rapid decline within one to two hours. We conclude that rIFN-gamma can be safely administered by a six-hour IV infusion and that it can induce in vivo some of the biologic effects reported in in vitro studies.

Phase I study of a combination of recombinant interferon-alpha and recombinant interferon-gamma in cancer patients.

1986 ◽  
Vol 4 (11) ◽  
pp. 1677-1683 ◽  
Author(s):  
R Kurzrock ◽  
M G Rosenblum ◽  
J R Quesada ◽  
S A Sherwin ◽  
L M Itri ◽  
...  
Keyword(s):  
Interferon Gamma ◽  
Interferon Alpha ◽  
Maximum Tolerated Dose ◽  
Blood Levels ◽  
Recombinant Interferon ◽  
Starting Dose ◽  
The Individual ◽  
Dose Levels ◽  
Recombinant Interferon Alpha

Combinations of interferon-alpha and interferon-gamma demonstrate synergistic antiviral and anti-proliferative activity in vitro. Therefore, we initiated a clinical study of combination interferon therapy in humans. Eighteen patients with metastatic solid tumors received daily intramuscular (IM) injections of recombinant interferon-alpha-A (IFN alfa-2a, Roferon-A; Hoffman-LaRoche, Nutley, NJ) and recombinant IFN-gamma (rIFN-gamma) for 6 weeks. The dose levels were 0.5, 1.0, 2.0, and 5.0 X 10(6) U/m2/d of each interferon. A minimum of two patients were entered sequentially at each dose level. Fever, chills, fatigue, and a greater than or equal to 50% drop in granulocyte counts were observed at all doses. Severity of symptoms corresponded to increasing dose levels. In contrast to the tachyphylaxis to these symptoms that usually develops in patients treated with the individual interferons, many patients on this study experienced persistent fever and worsening fatigue over 6 weeks. The maximum tolerated dose was 1 X 10(6) U/m2/d of each interferon. One patient with renal-cell carcinoma achieved a partial remission (duration, 3 months). Enzyme-linked immunoassay analysis in all four patients for whom complete data were available revealed that peak blood levels of IFN alfa-2a on day 22 were about tenfold higher than on day 1. Because of the possibility of cumulative toxicity, the recommended starting dose for further studies is 0.5 X 10(6) U/m2/d of each interferon, with escalation to 1.0 X 10(6) U/m2/d after 1 month if tolerance is acceptable. Phase II investigations to explore the antitumor efficacy of this regimen are planned.

Acoustic Examination of Preterm and Full-Term Infant Cries

1999 ◽  
Vol 42 (4) ◽  
pp. 850-861 ◽  
Author(s):  
Alexander M. Goberman ◽  
Michael P. Robb
Keyword(s):  
Preterm Infants ◽  
Newborn Infants ◽  
Term Infant ◽  
Speech Development ◽  
Full Term ◽  
Spectral Energy ◽  
Term Infants ◽  
Average Spectrum ◽  
Long Time ◽  
Infant Cries

The acoustic characteristics of crying behavior displayed in 2 groups of newborn infants are reported. The crying episodes of 10 full-term and 10 preterm infants were audio recorded and analyzed with regard to the long-time average spectrum (LTAS) characteristics. An LTAS display was created for each infant's non-partitioned crying episode, as well as for 3 equidurational partitions of the crying episode. Measures of first spectral peak, mean spectral energy, and spectral tilt were revealing of differences between full-term and preterm infants' non-partitioned crying episodes. In addition, the full-term infants demonstrated significant changes in their crying behavior across partitions, whereas the preterm infants changed little across the crying episode. Discussion focuses on possible differences between full-term and preterm infants in their neurophysiological maturity, and the subsequent impact on their speech development. The importance of examining entire crying episodes when evaluating the crying behavior of infants is also discussed.

Effects of Recombinant Interferon-Gamma and Interleukin-2 on the Generation of Lymphokine-Activated Killer Cells in Vitro

1990 ◽  
Vol 8 (5) ◽  
pp. 493-500 ◽  
Author(s):  
Harry W. Findley ◽  
Sherif Nasr ◽  
Zeinab Afify ◽  
Robert Hnath ◽  
Kathy Waldrep ◽  
...  
Keyword(s):  
Interferon Gamma ◽  
Interleukin 2 ◽  
Lymphokine Activated Killer Cells ◽  
Killer Cells ◽  
Recombinant Interferon

scholarly journals Lenalidomide and Pomalidomide Improve Function and Induce FcγRI/CD64 in Multiple Myeloma Neutrophils

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1455
Author(s):  
Alessandra Romano ◽  
Nunziatina Laura Parrinello ◽  
Marina Parisi ◽  
Vittorio Del Fabro ◽  
Angelo Curtopelle ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Phagocytic Activity ◽  
Bacterial Infections ◽  
Time Frame ◽  
Neutrophil Function ◽  
Secondary Prophylaxis ◽  
Newly Diagnosed ◽  
Increased Risk ◽  
Smoldering Myeloma

Background Myeloid dysfunction is an emerging hallmark of microenvironment changes occurring in multiple myeloma (MM). Our previous work showed that FcγRI/CD64 overexpression in neutrophils of newly diagnosed MM patients is associated to inferior outcomes, reduced oxidative bursts and phagocytosis, with an increased risk of bacterial infections. Pomalidomide is a novel immune-modulatory drug approved for relapsed/refractory patients (RRMM), with drug-related neutropenia as major limitation to treatment. Patients and methods Herein, we describe a prospective analysis of 51 consecutive RRMM patients treated with pomalidomide and dexamethasone (PomDex) from March 2015 through December 2016, associated with secondary prophylaxis with filgrastim (G-CSF) in case of neutrophil count <1500 cells/μL. Neutrophil function was investigated by flow cytometry, including the phagocytosis, oxidative bursts, and median fluorescence intensity of FcγRI-CD64. Controls included a group of newly diagnosed symptomatic MM (NDMM), asymptomatic (smoldering myeloma, MGUS) and healthy subjects referred to our Center in the same time-frame. Results Compared to controls, RRMM neutrophils had higher expression of FcγRI/CD64 and lower phagocytic activity and oxidative bursts. We maintained median leukocyte counts higher than 3.5· 10^9/L for 6 cycles, and median neutrophil counts higher than 1.5 · 10^9/L, with only 6 (11%) patients developing grade 3–4 infections, without pomalidomide dose reduction. After 4 cycles of PomDex, FcγRI/CD64 was further increased in neutrophils, and phagocytic activity and oxidative bursts recovered independently from filgrastim exposure and the quality of hematological responses. Similarly, in NDMM patients, lenalidomide but not bortezomib upregulated FcγRI/CD64 expression, improving phagocytic activity and oxidative bursta as tested in vitro. Conclusions Our combined biological and clinical data provide new information on the ability of pomalidomide and lenalidomide to modulate the functional activity of neutrophils, despite their chronic activation due to FcγRI/CD64 overexpression.

scholarly journals Diagnostic Accuracy of Biomarkers for Early-Onset Neonatal Bacterial Infections: Evaluation of Serum Procalcitonin Reference Curves

Diagnostics ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 839
Author(s):  
Hidetoshi Go ◽  
Nobuhiko Nagano ◽  
Daichi Katayama ◽  
Takuya Akimoto ◽  
Takayuki Imaizumi ◽  
...  
Keyword(s):  
Diagnostic Accuracy ◽  
Preterm Infants ◽  
Early Onset ◽  
Bacterial Infections ◽  
Immunoglobulin M ◽  
Youden Index ◽  
Reference Curve ◽  
Term Infants ◽  
Reference Curves ◽  
Wbc Count

To date, no clinical studies have compared the accuracy of serum procalcitonin (PCT) reference curves. We aimed to validate the diagnostic accuracy of previously reported serum PCT reference curves and to determine which biomarkers among a cut-off value over the 95th percentile in the serum PCT reference curve, white blood cell (WBC) count, and C-reactive protein (CRP) and immunoglobulin M (IgM) levels, have the highest diagnostic accuracy for early-onset neonatal bacterial infections. This retrospective cohort study assessed 16 preterm and 23 term infants with suspected bacterial infections within 72 h after birth. Each infant group was divided into two subgroups: confirmed- and non-infection. The diagnostic accuracy was determined using the Youden index. The reference curves by Fukuzumi et al. in preterm and term infants had the highest Youden indexes: 1.000 and 0.324, respectively. Among preterm infants, the Youden index for PCT was 1.000. Among term infants, the Youden index for a combination of PCT, CRP, and WBC and/or IgM was 1.000. In conclusion, a serum PCT level over the 95th percentile on the reference curve for preterm infants and a combination of PCT and CRP levels with WBC count and/or IgM levels for term infants provided sufficient diagnostic accuracy.

Formulation and Evaluation of Nanosponges loaded Bifonazole for Fun-gal Infection

2020 ◽  
Vol 18 ◽  
Author(s):  
Amaravathi Murali Krishna ◽  
Venkatesh Dinnekere Putte Gowda ◽  
Roopa Karki
Keyword(s):  
Drug Release ◽  
Fungal Infections ◽  
Skin Irritation ◽  
In Vitro Release ◽  
Three Dimensional ◽  
Entrapment Efficiency ◽  
In Vitro Drug Release ◽  
Model Stability ◽  
Novel Approach

Background: Nanosponges is a novel approach of topical drug delivery, especially for the fungal infections. Nanosponges are a unique class of nanoparticles with three-dimensional nanostructure in nanometers wide cavities, which can encapsulate both hydrophilic and lipophilic substances, will provide increased efficacy and safety. Objective: To formulate and evaluate Bifonazole loaded nanosponges in hydrogels for the treatment of fungal diseases. Methods: Bifonazole-loaded nanosponges to be formulated using emulsion solvent diffusion technique. Interaction of drugethyl cellulose polymer along with other excipients’ was done by using FTIR as well as DSC. The nanosponges formulations were evaluated with different parameters. Results: Bifonazole loaded nanosponges’ particle size and zeta potential for formulations were between the range of 183.7 to 560.2 nm and –17.77 to –21.9 mV, respectively. Surface morphology of nanosponges by SEM disclosed that it was spherical and porous in nature. Drug entrapment efficiency was found to be 45.44 to 79.71%. The drug release study was done by using phosphate buffer pH 6.8. Further in vitro release data is fitted in to kinetic models. The optimized formulation M6 has incorporated hydrogels, further evaluated skin irritation, in vitro drug release, viscosity and pH using a rat model. Stability studies of hydrogel formulation MH2 revealed that no changes in in-vitro drug release, pH and drug content study at the completion of 6 months. Conclusion: Thus, it indicated that the prepared Bifonazole loaded nanosponges into hydrogel was stable. Hence, it could be a suitable dosage form for the cure of fungal infections in the skin.

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